Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories: A CLL Research Consortium (CRC) Study

Nyla A. Heerema; John C. Byrd; Paola S. Dal Cin; Marie L. Dell' Aquila; Prasad R.K. Koduru; Ayala Aviram; Stephanie A. Smoley; Laura Z. Rassenti; Andrew W. Greaves; Jennifer R. Brown; Kanti R. Rai; Thomas J. Kipps; Neil E. Kay; Daniel L. Van Dyke

doi:10.1016/j.cancergencyto.2010.07.128

Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories: A CLL Research Consortium (CRC) Study

Nyla A. Heerema, John C. Byrd, Paola S. Dal Cin, Marie L. Dell' Aquila, Prasad R.K. Koduru, Ayala Aviram, Stephanie A. Smoley, Laura Z. Rassenti, Andrew W. Greaves, Jennifer R. Brown, Kanti R. Rai, Thomas J. Kipps, Neil E. Kay, Daniel L. Van Dyke

Research output: Contribution to journal › Article › peer-review

43 Scopus citations

Abstract

Cytogenetic abnormalities are important prognostic indicators in CLL. Historically, only interphase cytogenetics was clinically useful in CLL, because traditional mitogens are not effective mitotic stimulants. Recently, CpG-oligodeoxynucleotide (ODN) stimulation has shown effectiveness in CLL cells. The CLL Research Consortium tested the effectiveness and reproducibility of CpG-ODN stimulation for detecting chromosomally abnormal clones by five laboratories. More clonal abnormalities were observed after culture of CLL cells with CpG-ODN than with the traditional pokeweed mitogen plus 12- O-tetradecanoylphorbol-13-acetate (PWM+TPA). All clonal abnormalities in PWM+TPA cultures were observed in CpG-ODN cultures, whereas CpG-ODN identified some clones not found by PWM+TPA. CpG-ODN stimulation of one normal control sample and 12 CLL samples showed that, excepting clones of del(13q) in low frequencies and one translocation, results in all five laboratories were consistent, and all abnormalities were concordant with FISH. Abnormal clones in CLL were more readily detected with CpG-ODN stimulation than with traditional B-cell mitogens. With CpG-ODN stimulation, abnormalities were reproducible among cytogenetic laboratories. CpG-ODN did not appear to induce aberrations in cell culture, but did enhance detection of abnormalities and complexity in CLL. Because karyotypic complexity is prognostic and is not detectable by standard FISH analyses, stimulation with CpG-ODN is useful for identifying this additional prognostic factor in CLL.

Original language	English (US)
Pages (from-to)	134-140
Number of pages	7
Journal	Cancer Genetics and Cytogenetics
Volume	203
Issue number	2
DOIs	https://doi.org/10.1016/j.cancergencyto.2010.07.128
State	Published - Dec 2010

ASJC Scopus subject areas

Molecular Biology
Genetics
Cancer Research

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10.1016/j.cancergencyto.2010.07.128

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Heerema, N. A., Byrd, J. C., Dal Cin, P. S., Dell' Aquila, M. L., Koduru, P. R. K., Aviram, A., Smoley, S. A., Rassenti, L. Z., Greaves, A. W., Brown, J. R., Rai, K. R., Kipps, T. J., Kay, N. E., & Van Dyke, D. L. (2010). Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories: A CLL Research Consortium (CRC) Study. Cancer Genetics and Cytogenetics, 203(2), 134-140. https://doi.org/10.1016/j.cancergencyto.2010.07.128

Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories: A CLL Research Consortium (CRC) Study. / Heerema, Nyla A.; Byrd, John C.; Dal Cin, Paola S. et al.
In: Cancer Genetics and Cytogenetics, Vol. 203, No. 2, 12.2010, p. 134-140.

Research output: Contribution to journal › Article › peer-review

Heerema, NA, Byrd, JC, Dal Cin, PS, Dell' Aquila, ML, Koduru, PRK, Aviram, A, Smoley, SA, Rassenti, LZ, Greaves, AW, Brown, JR, Rai, KR, Kipps, TJ, Kay, NE & Van Dyke, DL 2010, 'Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories: A CLL Research Consortium (CRC) Study', Cancer Genetics and Cytogenetics, vol. 203, no. 2, pp. 134-140. https://doi.org/10.1016/j.cancergencyto.2010.07.128

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title = "Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories: A CLL Research Consortium (CRC) Study",

abstract = "Cytogenetic abnormalities are important prognostic indicators in CLL. Historically, only interphase cytogenetics was clinically useful in CLL, because traditional mitogens are not effective mitotic stimulants. Recently, CpG-oligodeoxynucleotide (ODN) stimulation has shown effectiveness in CLL cells. The CLL Research Consortium tested the effectiveness and reproducibility of CpG-ODN stimulation for detecting chromosomally abnormal clones by five laboratories. More clonal abnormalities were observed after culture of CLL cells with CpG-ODN than with the traditional pokeweed mitogen plus 12- O-tetradecanoylphorbol-13-acetate (PWM+TPA). All clonal abnormalities in PWM+TPA cultures were observed in CpG-ODN cultures, whereas CpG-ODN identified some clones not found by PWM+TPA. CpG-ODN stimulation of one normal control sample and 12 CLL samples showed that, excepting clones of del(13q) in low frequencies and one translocation, results in all five laboratories were consistent, and all abnormalities were concordant with FISH. Abnormal clones in CLL were more readily detected with CpG-ODN stimulation than with traditional B-cell mitogens. With CpG-ODN stimulation, abnormalities were reproducible among cytogenetic laboratories. CpG-ODN did not appear to induce aberrations in cell culture, but did enhance detection of abnormalities and complexity in CLL. Because karyotypic complexity is prognostic and is not detectable by standard FISH analyses, stimulation with CpG-ODN is useful for identifying this additional prognostic factor in CLL.",

author = "Heerema, {Nyla A.} and Byrd, {John C.} and {Dal Cin}, {Paola S.} and {Dell' Aquila}, {Marie L.} and Koduru, {Prasad R.K.} and Ayala Aviram and Smoley, {Stephanie A.} and Rassenti, {Laura Z.} and Greaves, {Andrew W.} and Brown, {Jennifer R.} and Rai, {Kanti R.} and Kipps, {Thomas J.} and Kay, {Neil E.} and {Van Dyke}, {Daniel L.}",

note = "Funding Information: This study was funded by CLL Research Consortium award P01 CA081534-07A1 .",

year = "2010",

month = dec,

doi = "10.1016/j.cancergencyto.2010.07.128",

language = "English (US)",

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T1 - Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories

T2 - A CLL Research Consortium (CRC) Study

AU - Heerema, Nyla A.

AU - Byrd, John C.

AU - Dal Cin, Paola S.

AU - Dell' Aquila, Marie L.

AU - Koduru, Prasad R.K.

AU - Aviram, Ayala

AU - Smoley, Stephanie A.

AU - Rassenti, Laura Z.

AU - Greaves, Andrew W.

AU - Brown, Jennifer R.

AU - Rai, Kanti R.

AU - Kipps, Thomas J.

AU - Kay, Neil E.

AU - Van Dyke, Daniel L.

N1 - Funding Information: This study was funded by CLL Research Consortium award P01 CA081534-07A1 .

PY - 2010/12

Y1 - 2010/12

N2 - Cytogenetic abnormalities are important prognostic indicators in CLL. Historically, only interphase cytogenetics was clinically useful in CLL, because traditional mitogens are not effective mitotic stimulants. Recently, CpG-oligodeoxynucleotide (ODN) stimulation has shown effectiveness in CLL cells. The CLL Research Consortium tested the effectiveness and reproducibility of CpG-ODN stimulation for detecting chromosomally abnormal clones by five laboratories. More clonal abnormalities were observed after culture of CLL cells with CpG-ODN than with the traditional pokeweed mitogen plus 12- O-tetradecanoylphorbol-13-acetate (PWM+TPA). All clonal abnormalities in PWM+TPA cultures were observed in CpG-ODN cultures, whereas CpG-ODN identified some clones not found by PWM+TPA. CpG-ODN stimulation of one normal control sample and 12 CLL samples showed that, excepting clones of del(13q) in low frequencies and one translocation, results in all five laboratories were consistent, and all abnormalities were concordant with FISH. Abnormal clones in CLL were more readily detected with CpG-ODN stimulation than with traditional B-cell mitogens. With CpG-ODN stimulation, abnormalities were reproducible among cytogenetic laboratories. CpG-ODN did not appear to induce aberrations in cell culture, but did enhance detection of abnormalities and complexity in CLL. Because karyotypic complexity is prognostic and is not detectable by standard FISH analyses, stimulation with CpG-ODN is useful for identifying this additional prognostic factor in CLL.

AB - Cytogenetic abnormalities are important prognostic indicators in CLL. Historically, only interphase cytogenetics was clinically useful in CLL, because traditional mitogens are not effective mitotic stimulants. Recently, CpG-oligodeoxynucleotide (ODN) stimulation has shown effectiveness in CLL cells. The CLL Research Consortium tested the effectiveness and reproducibility of CpG-ODN stimulation for detecting chromosomally abnormal clones by five laboratories. More clonal abnormalities were observed after culture of CLL cells with CpG-ODN than with the traditional pokeweed mitogen plus 12- O-tetradecanoylphorbol-13-acetate (PWM+TPA). All clonal abnormalities in PWM+TPA cultures were observed in CpG-ODN cultures, whereas CpG-ODN identified some clones not found by PWM+TPA. CpG-ODN stimulation of one normal control sample and 12 CLL samples showed that, excepting clones of del(13q) in low frequencies and one translocation, results in all five laboratories were consistent, and all abnormalities were concordant with FISH. Abnormal clones in CLL were more readily detected with CpG-ODN stimulation than with traditional B-cell mitogens. With CpG-ODN stimulation, abnormalities were reproducible among cytogenetic laboratories. CpG-ODN did not appear to induce aberrations in cell culture, but did enhance detection of abnormalities and complexity in CLL. Because karyotypic complexity is prognostic and is not detectable by standard FISH analyses, stimulation with CpG-ODN is useful for identifying this additional prognostic factor in CLL.

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Stimulation of chronic lymphocytic leukemia cells with CpG oligodeoxynucleotide gives consistent karyotypic results among laboratories: A CLL Research Consortium (CRC) Study

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